Abstract Polyethylene glycol (PEG) is widely used to sterically stabilize liposomes and improve the pharmacokinetic profile of drugs, peptides and nanoparticles. Here we report that ammonium sulfate (AS) can evoke the aggregation of {PEGylated} vesicles in a concentration-dependent manner. Liposomes with 5 mol% {PEG} were colloidally stable at {AS} concentrations up to 0.7 mM, above which they precipitated and formed micron-size aggregates with irregular shape. While aggregation was reversible up to 0.9 M of AS, above 1 M fusion occurred, which irreversibly distorted the size distribution. Zeta potential of liposomes markedly increased from −71 ± 2.5 mV to 2 ± 0.5 mV upon raising the {AS} concentration from 0 to 0.1 M, but no considerable increase was seen during further {AS} addition, showing that the aggregation is independent of surface charge. There was no aggregation in the absence of the {PEG} chains, and increasing {PEG} molar% shifted the aggregation threshold to lower {AS} concentrations. Changes in the {FTIR} spectral features of {PEGylated} vesicles suggest that {AS} dehydrates {PEG} chains. Other kosmotropic salts also led to aggregation, while chaotropic salts did not, which indicates a general kosmotropic phenomenon. The driving force behind aggregation is likely to be the hydrophobic effect due to salting out the polymer similarly to what happens during protein purification or Hydrophobic Interaction Chromatography. Since liposome aggregation and fusion may result in difficulties during formulation and adverse reaction upon application, the phenomena detailed in this paper may have both technological and therapeutical consequences.